This proposal investigates the neural circuitry that integrates input from the adiposity hormone, leptin, and the gut-derived satiety signals, cholecystokinin (CCK), in the control of food intake. Available data provides compelling support for the hypothesis that leptin reduces food intake in part by enhancing satiety and hindbrain responses to gastrointestinal signals, including CCK. Here, we propose to identify the specific subset of hindbrain neurons whose responses to CCK are stimulated by leptin. Second, we will determine whether the interaction between leptin and CCK, clearly demonstrated with pharmacological doses of leptin, occurs with physiological changes in leptin levels. Finally, we will determine whether leptin regulates hindbrain cell responsiveness to CCK through a direct action within the caudal brainstem or through an indirect route, perhaps involving a descending projection from the forebrain. Together, these studies will help to clarify how changes in body fat stores lead to compensatory adjustments of meal size and thus have the potential to significantly advance our understanding of the neural circuitry that regulates energy balance. [unreadable] [unreadable]